A number of aromatic diamidines have been shown to bind to the minor-groove of DNA, and to exhibit useful antimicrobial activity. Various hypotheses of the mode of antimicrobial action of the aryl amidines have been proposed. However, evidence is growing that these compounds function by complex formation with DNA and subsequent selective inhibition of DNA dependent microbial enzymes. Intervention in transcription control has been demonstrated and seems to be a plausible mode of action for structurally diverse minor groove binders. (Das, B. P.; Boykin, D. W., J. Med. Chem. 1977, 20, 531-536; Boykin, D. W. et al., J. Med. Chem. 1995, 36, 912-916; Kumar, A. et al., Eur. J. Med. Chem. 1996, 31, 767-773; Lombardy, R. J. et al., J. Med. Chem. 1996, 31, 912-916; Tidwell, R. R. et al., Antimicrob. Agents Chemother. 1993, 37, 1713-1716; Tidwell, R. R.; Bell, C. A., Pentamidine and Related Compounds in Treatment of Pneumocystis carinii Infection, in Pneumocystis carinii, Ed Marcel Decker; New York, 1993, 561-583; Henderson, D.; Hurley, L. H., Nature Med. 1995, 1, 525-527; Mote, J. Jr., et al., J. Mol. Biol. 1994, 226, 725-737; Boykin, D. W., et al., J. Med. Chem. 1998, 41, 124-129).
PCT Application No. WO96/40117 (Dec. 19, 1996) describes dicationic substituted carbazoles and the use thereof in treating Pneumocystis carinii pneumonia (PCP), Cryptococcus neoformans, Cryptosporidium parvum, and Candida albicans.
J. Moffatt, J. Chem. Soc. 1951, 625-626, describes 3:6-diamidinodibenzofuran, and the use thereof in the treatment of as a trypanocide.